Niacin Attenuates Pulmonary Hypertension Through H-PGDS in Macrophages

Daile Jia, Peiyuan Bai, Naifu Wan, Jiao Liu, Qian Zhu, Yuhu He, Guilin Chen, Jing Wang, Han Chen, Chen Wang, Ankang Lyu, Michael Lazarus, Yunchao Su, Yoshihiro Urade, Ying Yu, Jian Zhang, Yujun Shen

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Rationale: Pulmonary arterial hypertension (PAH) is characterized by progressive pulmonary vascular remodeling, accompanied by varying degrees of perivascular inflammation. Niacin, a commonly used lipid-lowering drug, possesses vasodilating and proresolution effects by promoting the release of prostaglandin D2(PGD2). However, whether or not niacin confers protection against PAH pathogenesis is still unknown. Objective: This study aimed to determine whether or not niacin attenuates the development of PAH and, if so, to elucidate the molecular mechanisms underlying its effects. Methods and Results: Vascular endothelial growth factor receptor inhibitor SU5416 and hypoxic exposure were used to induce pulmonary hypertension (PH) in rodents. We found that niacin attenuated the development of this hypoxia/SU5416-induced PH in mice and suppressed progression of monocrotaline-induced and hypoxia/SU5416-induced PH in rats through the reduction of pulmonary artery remodeling. Niacin boosted PGD2generation in lung tissue, mainly through H-PGDS (hematopoietic PGD2synthases). Deletion of H-PGDS, but not lipocalin-type PGDS, exacerbated the hypoxia/SU5416-induced PH in mice and abolished the protective effects of niacin against PAH. Moreover, H-PGDS was expressed dominantly in infiltrated macrophages in lungs of PH mice and patients with idiopathic PAH. Macrophage-specific deletion of H-PGDS markedly decreased PGD2generation in lungs, aggravated hypoxia/SU5416-induced PH in mice, and attenuated the therapeutic effect of niacin on PAH. Conclusions: Niacin treatment ameliorates the progression of PAH through the suppression of vascular remodeling by stimulating H-PGDS-derived PGD2release from macrophages.

Original languageEnglish (US)
Pages (from-to)1323-1336
Number of pages14
JournalCirculation research
Issue number10
StatePublished - Oct 23 2020


  • macrophage
  • niacin
  • pulmonary arterial hypertension
  • pulmonary artery remodeling

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine


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